Integrated valve assembly and method of delivering and deploying an integrated valve assembly

ABSTRACT

An integrated valve prosthesis includes an anchor stent, a tether component, and a valve component. The anchor stent includes a self-expanding tubular frame member configured to be deployed in the annulus of an aortic valve or the aorta. The valve component includes a valve frame and a prosthetic valve coupled to the valve frame, and is configured to be deployed within the anchor stent. The tether component includes a first end coupled to the anchor stent and a second end coupled to the valve frame. In the delivery configuration, the tether component extends in a first direction from the anchor stent to the valve component, and in the deployed configuration, the tether component extends in a second direction from the anchor stent to the valve component. The second direction is generally opposite the first direction. The tether component may set the location of the valve component relative to the anchor stent.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.17/017,382, filed Sep. 19, 2020, which is a division of U.S. patentapplication Ser. No. 16/023,475, filed Jun. 29, 2018, now U.S. Pat. No.10,799,343, which is a division of U.S. patent application Ser. No.15/013,341, filed Feb. 2, 2016, which claims priority under 35 U.S.C.119(e) to the benefit of the filing date of U.S. Provisional ApplicationNo. 62/115,464 filed Feb. 12, 2015, the contents of both of which areincorporated herein by reference in their entirety.

FIELD OF THE INVENTION

Embodiments hereof relate to heart valve prostheses and methods forintraluminally deploying heart valve prostheses, and in particular, toan integrated heart valve prosthesis including an anchor stent connectedto a valve component and methods of intraluminally delivering anddeploying the integrated valve prosthesis.

BACKGROUND OF THE INVENTION

Heart valves, such as the mitral, tricuspid, aortic, and pulmonaryvalves, are sometimes damaged by disease or by aging, resulting inproblems with the proper functioning of the valve. Heart valve problemsgenerally take one of two forms: stenosis in which a valve does not opencompletely or the opening is too small, resulting in restricted bloodflow; or insufficiency in which blood leaks backward across a valve whenit should be closed.

Heart valve replacement has become a routine surgical procedure forpatients suffering from valve regurgitation or stenotic calcification ofthe leaflets. Conventionally, the vast majority of valve replacementsentail full sternotomy in placing the patient on cardiopulmonary bypass.Traditional open surgery inflicts significant patient trauma anddiscomfort, requires extensive recuperation times, and may result inlife-threatening complications.

To address these concerns, efforts have been made to perform cardiacvalve replacements using minimally-invasive techniques. In thesemethods, laparoscopic instruments are employed to make small openingsthrough the patient's ribs to provide access to the heart. Whileconsiderable effort has been devoted to such techniques, widespreadacceptance has been limited by the clinician's ability to access onlycertain regions of the heart using laparoscopic instruments.

Still other efforts have been focused upon percutaneous transcatheter(or transluminal) delivery of replacement cardiac valves to solve theproblems presented by traditional open surgery and minimally-invasivesurgical methods. In such methods, a valve prosthesis is compacted fordelivery in a catheter and then advanced, for example through an openingin the femoral artery and through the descending aorta to the heart,where the prosthesis is then deployed in the valve annulus (e.g., theaortic valve annulus).

Various types and configurations of prosthetic heart valves are used inpercutaneous valve procedures to replace diseased natural human heartvalves. The actual shape and configuration of any particular prostheticheart valve is dependent to some extent upon the valve being replaced(i.e., mitral valve, tricuspid valve, aortic valve, or pulmonary valve).In general, prosthetic heart valve designs attempt to replicate thefunction of the valve being replaced and thus will include valveleaflet-like structures used with either bioprostheses or mechanicalheart valve prostheses. If bioprostheses are selected, the replacementvalves may include a valved vein segment or pericardial manufacturedtissue valve that is mounted in some manner within an expandable stentframe to make a valved stent. In order to prepare such a valve forpercutaneous implantation, one type of valved stent can be initiallyprovided in an expanded or uncrimped condition, then crimped orcompressed around a balloon portion of a catheter until it is close tothe diameter of the catheter. In other percutaneous implantationsystems, the stent frame of the valved stent can be made of aself-expanding material. With these systems, the valved stent is crimpeddown to a desired size and held in that compressed state within asheath, for example. Retracting the sheath from this valved stent allowsthe stent to expand to a larger diameter, such as when the valved stentis in a desired position within a patient.

While some problems of traditional open-heart surgery are overcome bypercutaneous transcatheter (transluminal) methods, there are still risksassociated with the method including patient prosthetic mismatch (PPM),para-valvular leakage, and conductance disorders. Many of thesepotential risks are thought to be aggravated by improper valveplacement.

Patient prosthetic mismatch (PPM) is when an effective prosthetic valvearea is less than that of a normal human valve. Despite technicalefforts to optimize valve prostheses, their rheological properties arenot comparable with those of native human valves and aortic stenosiswill occur in a normally functioning prosthesis that is too small forthe patient. Patient prosthetic mismatch is associated with decreasedregression of left ventricular hypertrophy, reduced coronary flowreserve, increased incidence of congestive heart failure, diminishedfunctional capacity, and increased risk of early and late mortality.Implantation of a prosthetic heart valve at an inaccurate depth isthought to increase the incidence and severity of patient prostheticmismatch.

Para-valvular leakage (PVL) is leakage around an implanted prostheticvalve. The effects of para-valvular leakage on patients range from smallPVL resulting in valve inefficiency and intravascular hemolysis causinganemia, to large PVL resulting in risk of heart failure andendocarditis. Often, sealing material is secured to the inside oroutside of the stent frame to reduce the incidence of PVL, but thesealing material increases overall diameter (crossing profile) of theradially collapsed stent which limits crimping and may limit accessthrough some vessels. Implantation of a prosthetic heart valve at aninaccurate depth is also thought to increase the incidence and severityof para-valvular leakage.

Conductance disorder is the abnormal progression of electrical impulsesthrough the heart causing the heart to beat in an irregular fashion. Theabnormal impulses may exhibit themselves as a mismatch of the electricalsignals between sides or top to bottom and may cause symptoms fromheadaches, dizziness, and arrhythmia to cardiac arrest. Valve prosthesesimplanted too deep are thought to be more prone to inducing conductiondisorders.

There is a need for devices and methods that allow for reduced crossingprofile of a percutaneous transcatheter (transluminal) delivery ofreplacement heart valves while also providing sealing material to reducepara-valvular leakage (PVL). There is also a need for devices andmethods to accurately locate and deploy valve prostheses to minimizepara-valvular leakage (PVL), patient prosthesis mismatch (PPM), andconductance disorders in patients undergoing transcatheter valveimplantation procedures.

BRIEF SUMMARY OF THE INVENTION

Embodiments hereof are related to an integrated valve assembly includingan anchor stent, a tether component, and a valve component sequentiallyarranged within a delivery device. The anchor stent includes aself-expanding tubular frame member configured to be deployed in theannulus of an aortic valve. The valve component includes a valve frameconfigured to be deployed within the tubular frame member of the anchorstent such that the valve frame engages with the attachment members ofthe tubular frame member and a prosthetic valve coupled to the valveframe. The tether component is a plurality of tethers with a first endof the tether component coupled to the anchor frame and a second end ofthe tether component coupled to the valve frame. In the deliveryconfiguration, the tether component extends in a first direction fromthe anchor stent to the valve component, and in the deployedconfiguration, the tether component extends in a second direction fromthe anchor stent to the valve component. The second direction isgenerally opposite the first direction.

Embodiments hereof are also directed to a method of implanting anintegrated valve assembly at a location of a native heart valve. In anembodiment, the integrated valve assembly including an anchor stent, avalve component, and a tether component having a first end coupled tothe anchor stent and a second end coupled to the valve component, isadvanced in a delivery system in a radially compressed configurationinto the annulus of a heart valve. The anchor stent includes a tubularframe member. The anchor stent is deployed in the annulus of the heartvalve such that the tubular frame member expands from the radiallycompressed configuration to a radially expanded configuration engagingan inner wall surface of the annulus. Next, the tether component isexposed from the delivery system. The delivery system is advancedthrough the lumen of the anchor stent, effectively flipping thedirection of the tether component. Accordingly, whereas the tethercomponent in the delivery system initially extends in a first directionfrom the anchor stent towards the valve component, once flipped, thetether component extends in a second direction generally opposite fromthe first direction from the anchor stent towards the valve component.The delivery device is advanced until the tether component is taut.Tautness of the tether component correctly positions the valve componentfor deployment within the anchor stent. The valve component is thendeployed. The valve component includes a valve frame and a prostheticvalve coupled to the valve frame. The valve component is deployed at thenative aortic valve such that the valve frame expands from a radiallycompressed configuration to a radially expanded configuration with aproximal portion of the valve frame engaging an inner surface of theanchor stent.

In another embodiment, an integrated valve assembly includes an anchorstent, a valve component, a tether component, and a skirt. The tethercomponent includes a first end coupled to the anchor stent, and a secondend coupled to the skirt. The skirt has a first end coupled to thetether component and a second end coupled to the valve component. Theintegrated valve assembly is advanced in a radially compressedconfiguration into the aorta. The anchor stent includes a tubular framemember and a proximal arm component extending from a proximal end of thetubular frame member. The proximal arm component is deployed such thatthe proximal arm component expands from a radially compressedconfiguration to the radially expanded configuration engaging the innerwall surface of the aortic sinuses. The anchor stent is advanced untilthe proximal arm component bottoms at the nadir of the aortic valveleaflets. The anchor stent is deployed in the aorta near the sinotubularjunction such that the tubular frame member expands from the radiallycompressed configuration to a radially expanded configuration engagingan inner wall surface of the ascending aorta. The tether component andskirt are released from the delivery system. The delivery system withthe valve component disposed therein is advanced through the lumen ofthe anchor stent, effectively flipping the direction of the tethers andskirt. Accordingly, whereas the tether component and the skirt initiallyextend in a first direction from the anchor stent towards the valvecomponent, once flipped, the tethers and skirt extend in a second, andgenerally opposite direction from the anchor stent towards the valvecomponent. The delivery system is advanced until the tether componentand the skirt are taut. Tautness of the tether component and the skirtcorrectly positions the valve component for deployment within theannulus of the native valve. The valve component includes a valve frameand a prosthetic valve coupled to the valve frame. The valve componentis deployed at the native aortic valve such that the valve frame expandsfrom a radially compressed configuration to a radially expandedconfiguration with a proximal portion of the valve frame engaging thenative aortic annulus and a distal portion of the valve frame engagingan inner surface of the anchor stent.

BRIEF DESCRIPTION OF DRAWINGS

The foregoing and other features and advantages of the invention will beapparent from the following description of embodiments hereof asillustrated in the accompanying drawings. The accompanying drawings,which are incorporated herein and form a part of the specification,further serve to explain the principles of the invention and to enable aperson skilled in the pertinent art to make and use the invention. Thedrawings are not to scale.

FIG. 1 is a schematic illustration of a prior art stented valveprosthesis.

FIG. 2 is a schematic illustration of the prior art stented valveprosthesis of FIG. 1 .

FIG. 3 is a schematic illustration of an integrated prosthesis assemblyin accordance with an embodiment hereof.

FIGS. 3A and 3B are a schematic cross-sectional illustrations ofembodiments of an anchor stent with filler material on an inside surfaceor outside surface thereof.

FIG. 4 is a schematic illustration of an integrated prosthesis assemblyin accordance with another embodiment hereof.

FIGS. 5-11, and 11A are schematic illustrations of an embodiment of amethod for delivering and deploying the integrated prosthesis assemblyof FIG. 3 at an aortic valve with the anchor stent deployed in theannulus.

FIG. 12 is a schematic illustration of the integrated valve prosthesisassembly of FIG. 4 deployed at an aortic valve according to the methodof FIGS. 5-11A.

FIG. 13 is a schematic illustration of the integrated valve prosthesisassembly of FIG. 4 deployed at an aortic valve with the skirt componenteverted.

FIG. 14 is a schematic illustration of an integrated valve assembly inaccordance with another embodiment hereof.

FIG. 14A is a schematic illustration of an anchor stent of theintegrated valve assembly of FIG. 14 .

FIG. 15 is a schematic illustration of a distal portion of a deliverydevice with the integrated valve assembly of FIG. 14 disposed therein.

FIGS. 16-23 are schematic illustrations of an embodiment of a method fordelivering and deploying the integrated valve assembly of FIG. 14 at anaortic valve with the anchor stent deployed in the aorta.

DETAILED DESCRIPTION OF THE INVENTION

Specific embodiments of the present invention are now described withreference to the figures, wherein like reference numbers indicateidentical or functionally similar elements. The terms “distal” and“proximal” when used in the following description to refer to a catheteror delivery system are with respect to a position or direction relativeto the treating clinician. Thus, “distal” and “distally” refer topositions distant from or in a direction away from the clinician and“proximal” and “proximally” refer to positions near or in a directiontoward the clinician. When the terms “distal” and “proximal” are used inthe following description to refer to a device to be implanted into avessel, such as an anchor stent or valve component, they are used withreference to the direction of blood flow from the heart. Thus, “distal”and “distally” refer to positions in a downstream direction with respectto the direction of blood flow and “proximal” and “proximally” refer topositions in an upstream direction with respect to the direction ofblood flow.

FIGS. 1 and 2 show an exemplary conventional valve prosthesis similar tothe Medtronic CoreValve® transcatheter aortic valve replacement valveprosthesis and as described in U.S. Patent Application Publication No.2011/0172765 to Nguyen et al. (hereinafter “the '765 publication”),which is incorporated by reference herein in its entirety. As shown inFIGS. 1 and 2 , valve prosthesis 100 includes an expandable frame 102having a valve body 104 affixed to its interior surface, e.g., bysutures. Frame 102 preferably comprises a self-expanding structureformed by laser cutting or etching a metal alloy tube comprising, forexample, stainless steel or a shape memory material such as nickeltitanium. The frame has an expanded deployed configuration which isimpressed upon the metal alloy tube using techniques known in the art.Valve body 104 preferably comprises individual leaflets assembled to askirt, where all of the components are formed from a natural or man-madematerial, including but not limited to, mammalian tissue, such asporcine, equine or bovine pericardium, or a synthetic or polymericmaterial.

Frame 102 in the exemplary embodiment includes an outflow section 106,an inflow section 110, and a constriction region 108 between the inflowand outflow sections. Frame 102 may comprise a plurality of cells havingsizes that vary along the length of the prosthesis. When configured as areplacement for an aortic valve, inflow section 110 extends into andanchors within the aortic annulus of a patient's left ventricle andoutflow section 106 is positioned in the patient's ascending aorta.Frame 102 also may include eyelets 130 for use in loading the heartvalve prosthesis 100 into a delivery catheter.

Valve body 104 may include a skirt 121 affixed to frame 102, andleaflets 112, 114, 116. Leaflets 112, 114, 116 may be attached alongtheir bases to skirt 121, for example, using sutures or a suitablebiocompatible adhesive. Adjoining pairs of leaflets are attached to oneanother at their lateral ends to form commissures 124, 126, 128, withfree edges 118, 120, 122 of the leaflets forming coaptation edges thatmeet in an area of coaptation, as described in the '765 application andshown in FIG. 2 hereof.

The following detailed description is merely exemplary in nature and isnot intended to limit the invention or the application and uses of theinvention. Although the description of the invention is in the contextof transcatheter aortic valve implantation, the invention may also beused in any other body passageways where it is deemed useful.Furthermore, there is no intention to be bound by any expressed orimplied theory presented in the preceding technical field, background,brief summary or the following detailed description.

Embodiments hereof are related to an integrated valve assembly includingan anchor stent, a tether component, and a valve component assembled andconnected together outside the human body. The tether component may be aplurality of tethers, a cylindrical skirt or a combination of thereof.

In an embodiment shown in FIG. 3 , an integrated valve assembly 300includes an anchor stent 210, a tether component 301 and a valvecomponent 240. Valve component 240 is sized and shaped to fit within alumen of anchor stent 210, and anchor stent 210 is designed to deploywithin the annulus of a heart valve, as described in more detail below.

Anchor stent 210 includes a frame 212 having a proximal end 216 and adistal end 214, as shown in FIG. 3 . Frame 212 is a generally tubularconfiguration having a lumen 213. Frame 212 is a stent structure as isknown in the art. Frame 212 may be self expanding or may be balloonexpandable. Generally, frame 212 includes a first, radially compressedconfiguration for delivery and a second, radially expanded or deployedconfiguration when deployed at the desired site. In the radiallyexpanded configuration, frame 212 may have a diameter in the range of 23to 29 millimeters for use in the aortic annulus. However, it isrecognized that frame 212 may have a smaller or larger expanded diameterdepending on the application. Further, the unrestrained expandeddiameter of self-expanding frames, such as frame 212, is generally about2-5 millimeters larger than the diameter of the location in which theframe is to be installed, in order to create opposing radial forcesbetween the outward radial force of the frame against an inwardresisting force of the vessel.

Anchor stent 210 may include a filler material 211 on an outside 213surface of anchor stent 210, as shown in FIG. 3A, or the inside surface215 of anchor stent 210, as shown in FIG. 3B, or both surfaces (notshown). Filler material 211 may be any anti-para-valvular leakagematerial suitable for the purposes described herein, such as, but notlimited to, polyethylene terephthalate (PET), tissue (including porcineor bovine pericardium), or other biocompatible materials. The materialmay be woven or knitted. Filler material 211 may be secured to anchorstent 210 by methods such as, but not limited to, adhesives, sutures,laser or ultrasonic welding, or any other methods suitable for thepurposes described herein.

Tether component 301 includes a plurality of tethers 302 as shown inFIG. 3 . The embodiment of FIG. 3 shows three (3) tethers 302, however,it is understood that more or fewer tethers 302 may be provideddepending on the specific requirements of the components, devices, andprocedures being utilized. Tether component 301 has a first end 304coupled to anchor stent 210, a second end 306 coupled to valve component240, and a length that provides proper location placement of valvecomponent 240 at the implantation site, as described in greater detailbelow. Tethers 302 are elongated members such as wires or sutures andmay be constructed of materials such as, but not limited to, stainlesssteel, Nitinol, nylon, polybutester, polypropylene, silk, and polyesteror other materials suitable for the purposes described herein. Tethers302 may be connected to anchor frame 212 and valve frame 242 by methodssuch as, but not limited to fusing, welding, sutures or otherwise tied.

Valve component 240 includes a frame 242 and a prosthetic valve 250.Frame 242 is a generally tubular configuration having a proximal end246, a distal end 244, and a lumen 243 there between. Frame 242 is astent structure as is known in the art, and may be self-expanding orballoon expandable. Generally, frame 242 includes a first, radiallycompressed configuration for delivery and a second, radially expanded ordeployed configuration when deployed at the desired site. In theradially expanded configuration, frame 242 may have a diameter in therange of 23 to 31 millimeters. However, it is recognized that frame 242may have a smaller or larger expanded diameter depending on theapplication. Further, the unrestrained expanded diameter ofself-expanding frames, such as frame 242, is generally about 2-5millimeters larger than the diameter of the location in which the frameis to be installed, in order to create opposing radial forces betweenthe outward radial force of the frame against an inward resisting forceof the vessel. In the embodiment shown, distal end 244 has a largerexpanded diameter than proximal end 246, similar to valve prosthesis 100shown in FIGS. 1-2 . However, frame 242 is not limited to such aconfiguration, and instead may have proximal and distal ends withsimilar expanded diameters. Further, frame 242 may have a smaller orlarger expanded diameter depending on the application. Valve component240 is configured to be disposed such that prosthetic valve 250 isdisposed approximately at the location of the native aortic valve.

As explained briefly above and in more detail below, integrated valveassembly 300 includes anchor stent 210, tether component 301, and valvecomponent 240. Anchor stent 210 is configured to be disposed in theannulus of the aortic valve. Valve component 240 is configured to bedisposed such that prosthetic valve 250 is disposed approximately at thelocation of the native aortic valve with proximal end 246 of frame 242separating the valve leaflets of the native aortic valve. Proximal end246 of frame 242 extends into lumen 213 of frame 212 of anchor stent 210and is held in place by the outward radial force of frame 242 andfrictional forces between frame 242 of valve component 240 and frame 212of anchor stent 210. Further, an inner surface of frame 212 and/or anouter surface of frame 242 may include locking features such as barbs,anti-migration tabs or other devices known to those skilled in the artto interconnect with anchor frame 212 and/or filler material 211

FIG. 4 shows another embodiment of an integrated valve assembly 320including anchor stent 210, a tether component 321 comprising acylindrical skirt 322, and a valve component 240. Anchor stent 210 andvalve component 240 may be as described above with respect to theembodiment of FIG. 3 . Skirt 322 has a first end 324 coupled to anchorstent 210, a second end 326 coupled to valve component 240, and a lengththat provides proper placement of valve component 240 at theimplantation site, as described in greater detail below. Skirt 322 is acylindrical tube constructed of cloth or fabric material. The fabric maycomprise any suitable material including, but not limited to, wovenpolyester such as polyethylene terephthalate, polytetrafluoroethylene(PTFE), tissue (such as porcine or bovine pericardium, or otherbiocompatible materials. Skirt 322 is secured to anchor frame 212 andvalve frame 242 in a manner such as, but not limited to sutures, laseror ultrasonic welding, or other methods suitable for the purposesdisclosed herein.

While embodiments of FIGS. 3 and 4 provide possible configurations for atether component, they are not meant to limit the component to theseconfigurations, and other materials, shapes, and combinations of skirtsand/or tethers may be utilized. For example, and not by way oflimitation, a skirt may be attached to an inside surface or outsidesurface of the tethers, or the tethers and the skirt may be connectedsequentially. For example, and not by way of limitation, the tethers maybe attached to the anchor stent and to the skirt with the skirt attachedto the tethers and to the valve component.

FIGS. 5-11 and 11A schematically represent a method of delivering anddeploying an integrated valve assembly in accordance with an embodimenthereof FIGS. 5-11A describe the method with respect to integrated valveassembly 300 of FIG. 3 . FIGS. 5-11A are not drawn to scale regardingrelative lengths of anchor stent 210 and valve component 240.

FIG. 5 shows a guidewire 502 advanced distally, i.e., away from theclinician, through the aorta 400 into the aortic sinuses 412 in theregion of the aortic valve 414. Guidewire 502 may be introduced throughan opening or arteriotomy through the wall of femoral artery in thegroin region of the patient by methods known to those skilled in theart, such as, but not limited to, the Seldinger technique. Guidewire 502is advanced into the descending (or abdominal) aorta 406, the aorticarch 404, and the ascending aorta 402, as shown in FIG. 5 . FIG. 5 alsoshows three branch arteries emanating from aortic arch 404. Inparticular, the innominate or brachiocephalic artery 416, the leftcommon carotid artery 418, and the left subclavian artery 420 emanatefrom aortic arch 404. The brachiocephalic artery 416 branches into theright common carotid artery and the right subclavian artery. AlthoughFIGS. 5-11A show a retrograde percutaneous femoral procedure, it is notmeant to limit the method of use and other procedural methods may beused. For example, and not by way of limitation, retrograde percutaneousimplantation via subclavian/axillary routes, direct apical puncture, andthe use of direct aortic access via either ministernotomy or rightanterior thoracotomy may also be used.

FIG. 6 shows a delivery system 500 for delivering integrated valveassembly 300 being advanced distally, i.e., away from the clinician,over guidewire 502 to a location in the annulus 415 of aortic valve 414.Delivery system 500 may be any suitable delivery system for deliveringstents and/or stent grafts. In the embodiment shown schematically,anchor stent 210 is a self-expanding stent, tether component 301 is aplurality of tethers, and valve frame 242 of valve component 240 is aself-expanding stent. Accordingly, delivery system 500 generallyincludes an inner or guidewire shaft 508 which includes a guidewirelumen for receiving guidewire 502. A proximal end of guidewire 502 maybe backloaded into the guidewire lumen of inner shaft 508 through adistal opening in inner shaft 508. Delivery system 500 may be anover-the-wire type catheter, or a rapid exchange catheter, or othercatheter devices. Delivery system 500 further generally may include adistal tip 501, an outer sheath 504 that maintains anchor stent 210 andvalve component 240 in the radially compressed or delivery configurationduring intraluminal delivery through the vasculature, as shown in FIG. 6and may also include a pusher or stopper 506, and other features.Delivery system 500 and/or anchor stent 210 may also include, forexample, radiopaque markers such that the clinician may determine whendelivery system 500 and/or anchor stent 210 is in the proper locationfor deployment.

Once delivery system 500 has been advanced to the desired location, suchas when proximal end 216 of anchor stent is generally aligned withannulus 415, outer sheath 504 is retracted proximally, i.e., towards theclinician, as shown in FIG. 7 . As outer sheath 504 is retracted, anchorframe 212 of anchor stent 210 expands radially outward, engaging theinner wall of annulus 415 of aortic valve 414, as shown in FIG. 7 .

Outer sheath 504 is further retracted proximally, i.e., towards theclinician, to deploy tether component 301 from outer sheath 504. Inother words, sheath 504 is retracted such that tether component 301 isno longer constrained by sheath 504. FIG. 7 shows tethers 302 deployeddistal of anchor stent 210 and extending in a first direction 520 fromanchor stent 210 toward valve frame 242.

With outer sheath 504 retracted such that anchor stent 210 is deployedat the annulus 415 and tethers 302 are released from outer sheath 504,delivery system 500 is advanced distally, i.e., away from the clinician,through lumen 213 of anchor frame 212, pulling tethers 302 into lumen213, effectively flipping the direction of tethers 302. Accordingly,whereas tethers 302 in FIG. 7 extend in a first direction 520 fromanchor stent 210 towards valve component 240, tethers 302 in FIGS. 8-9extend in a second direction 522 from anchor stent 210 towards valvecomponent 240. Second direction 522 is generally opposite firstdirection 520. The term “generally opposite” with respect to directionsdescribed herein and terms similar thereto, as used herein, is not sonarrow as to mean 180 degrees difference in direction. Instead, the term“generally opposite” with respect to direction means that a componentincludes a vector component in the first direction, the direction whichis generally opposite includes a vector component in the oppositedirection. Thus, the tethers 302 in the first direction 520 may bewithin 45 degrees of the first direction 520 and the second, generallyopposite direction may be within 135 degrees to 225 degrees of the firstdirection 520. With delivery system 500 advanced into lumen 213 ofanchor stent 210, tethers 302 reside within lumen 213 of anchor frame212. Delivery system 500 is advanced until tethers 302 are taut.Tautness of tethers 302 correctly positions valve component 240 fordeployment within anchor stent 210, as shown in FIGS. 8-9 . Anchor stent210 is shown with dotted lines for clarity of illustration in FIGS.8-11A.

With tethers 302 taut and valve component 240 in proper alignment withanchor stent 210, sheath 504 is further retracted proximally, i.e.,towards the clinician, and valve component 240 is deployed and expandsradially outward, engaging the inner wall of the anchor frame 212 andsinotubular junction 413, as shown in FIGS. 10-11A. With integratedvalve prosthesis assembly 300 fully deployed, delivery system 500 andguidewire 502 may be retracted proximally, i.e., towards the clinician,and removed in a manner consistent with current procedures know to thosein the art. Integrated valve prosthesis 300 remains in the fullydeployed configuration as shown in a close-up view of FIG. 11A.

While FIGS. 7-11A show the embodiment of FIG. 3 with tether component301 as a plurality of tethers 302, the method above would be equallyapplicable to the embodiment of FIG. 4 with skirt 322. FIG. 12 showsintegrated valve prosthesis 320 including skirt 322 deployed by themethod as described with respect to FIGS. 5-11A.

In another embodiment, integrated valve prosthesis 320 of FIG. 4 may bedeployed such that skirt 322 everts and is folded proximal of anchorstent 210, as shown in FIG. 13 . In such an embodiment, rather than thetautness of skirt 322 locating valve component 240, valve component 240may be located by conventional methods such as, but not limited to,x-ray fluoroscopy, ultrasound imaging, electromagnetic tracking, orother methods suitable for the purposes disclosed herein. In order todeploy skirt 322 as shown in FIG. 13 , the steps shown in FIGS. 5-7 areas described with respect to those figures. After skirt 322 is deployedas shown in FIG. 7 with respect to tethers 302, delivery system 500 isadvanced distally. However, due to the length of skirt 322, deliverysystem 500 and skirt 322 extend through and beyond anchor stent 210.Delivery system 500 is then retracted such that proximal end 246 ofvalve component 240 is disposed within anchor stent 210 and skirt 322folds as shown in FIG. 13 . The remaining steps for deploying valvecomponent 240 are as described with respect to FIGS. 10-11 .

The close-up views described above show lateral gaps between thedifferent parts which are disposed adjacent to each other. These gapsare shown for clarity such that the different parts of the integratedvalve prosthesis and the heart valve may be seen. It is understood thanmany of these parts will abut directly against each other due to theradially outward forces of anchor stent 210 and valve frame 242.

FIG. 14 shows schematically another embodiment of an integrated valveassembly 600 including an anchor stent 610, a plurality of tethers 602,a skirt 608, and a valve component 640. Valve component 640 is sized andshaped to fit within a lumen of anchor stent 610, and anchor stent 610is designed to deploy in the aorta, as described in more detail below.

Anchor stent 610 includes a frame 612 having a proximal end 616 and adistal end 614, and a proximal arm component 620 extending proximallyfrom proximal end 616 of frame 612, as shown in FIG. 14 . Frame 612 is agenerally tubular stent structure having a lumen 613, as describedpreviously. Frame 612 may be self-expanding or may be balloonexpandable. Generally, frame 612 includes a first, radially compressedconfiguration for delivery and a second, radially expanded or deployedconfiguration when deployed at the desired site. In the radiallyexpanded configuration, frame 612 may have a diameter in the range of 23to 31 millimeters. However, the expanded diameter may be a smaller orlarger depending on the application. Further, as known those skilled inthe art, the unrestrained expanded diameter of self-expanding frames,such as frame 612, is generally about 2-5 millimeters larger than thediameter of the vessel in which the frame is to be installed, in orderto create opposing radial forces between the outward radial force of theframe against an inward resisting force of the vessel.

Proximal arm component 620 extends proximally from proximal end 616 offrame 612. In the embodiment shown in FIG. 14 , proximal arm component620 includes a first arm 622, a second arm 624, and a third arm 626. Inthe embodiment shown in FIG. 14 , each arm 622, 624, 626 is in the formof a wire loop with first and second ends of the wire attached to frame612. In particular, first arm 622 includes first and second endsattached to frame 612 at connections 632, 633 respectively, as shown inFIG. 14A. Similarly, second arm 624 includes first and second endsattached to frame 612 at connections 628, 629, respectively, and thirdarm 626 includes first and second ends attached to frame 612 atconnections 630, 631, respectively. Connections 628, 629, 630, 631, 632,633 may be formed by the material of the arms and frame 612 fused orwelded together. Alternatively, the connections may be mechanicalconnections such as, but not limited to, sutured or otherwise tied, acrimp connector to crimp ends of the arms to frame 612, or othersuitable connections. Proximal arm component 620 includes a radiallycompressed configuration for delivery to the treatment site and aradially expanded or deployed configuration. In the radially expandedconfiguration, proximal arm component has a diameter in the range of 29to 39 mm. However, the diameter may be smaller or larger depending onthe application. As shown in FIG. 14, in the radially expandedconfiguration, arms 622, 624, and 626 flare outwardly from proximal end616 of frame 612. Although proximal arm component 620 has been shown ashaving three arms with connections approximately equally spaced aroundthe circumference of frame 612, more or fewer arms may be utilized, andthe arms need not be equally spaced around the circumference of frame612.

The embodiment of FIG. 14 shows three (3) tethers 602, however, it isunderstood that more or fewer tethers 602 may be provided depending onthe specific requirements of the components, devices and proceduresbeing utilized. Tethers 602 have a first end 604 coupled to anchor stent610, a second end 606 coupled to skirt 608, and a length that providesproper location placement of valve component 640 at the implantationsite, as described in greater detail below. Tethers 602 are elongatedmembers such as wires or sutures and may be constructed of materialssuch as, but not limited to, stainless steel, Nitinol, nylon,polybutester, polypropylene, silk, and polyester or other materialssuitable for the purposes described herein. Skirt 608 includes a firstend 609 connected to tethers 602 and a second end 607 connected to valvecomponent 640. In the embodiment shown, skirt 608 is a cylindrical tubeconstructed of cloth or fabric material. The fabric may comprise anysuitable material including, but not limited to, woven polyester such aspolyethylene terepthalate, polytetrafluoroethylene (PTFE), or otherbiocompatible material. Tethers 602 may be connected to anchor stent 610by tying, fusion, or other connectors that permit tethers 602 to move asdescribed below. Similarly, skirt 608 may be attached to valve component640 using sutures or other connectors that permit skirt 608 to moverelative to valve component 640, as described below. Tethers 602 may beattached to skirt 608 be tying or suturing tethers 602 to skirt 608, orby other connectors suitable for the purposes described herein.Additionally, the tethers 602 may be tied at a first end 604 coupled toanchor stent 610, tied to a second point on the end 606 of the skirt608, and tied to a third point 607 on valve component 640.

While the embodiment of FIG. 14 provides a possible configuration fortethers 602 and skirt 608, it is not meant to limit the component tothis configuration, and other materials, shapes and combinations ofskirts and/or tethers may be utilized depending on the application.

Valve component 640 includes a frame 642 and a prosthetic valve 650.Frame 642 is a generally tubular configuration having a proximal end646, a distal end 644, and a lumen 643 there between. Frame 642 may be astent structure as is known in the art. Frame 642 may be self-expandingor may be balloon expandable. Generally, frame 642 includes a first,radially compressed configuration for delivery and a second, radiallyexpanded or deployed configuration when deployed at the desired site. Inthe radially expanded configuration, frame 642 may have a diameter inthe range of 23 to 31 millimeters. In the embodiment shown in FIG. 14 ,distal end 644 and proximal end 646 of frame 642 have differentdiameters, similar to valve prosthesis 100 shown in FIG. 1 . However,distal end 644 and proximal end 646 may instead have similar expandeddiameters. Further, the diameter may be larger or smaller than the rangeprovided above depending on the application. Valve component 640 isconfigured to be disposed such that prosthetic valve 650 is disposedapproximately at the location of the native aortic valve.

As explained briefly above and in more detail below, integrated valveassembly 600 includes anchor stent 610, tethers 602, skirt 608, andvalve component 640. Anchor stent 610 is configured to be disposed inthe aorta, with proximal arm component 620 extending into the aorticroot or aortic sinuses. Valve component 640 is configured to be disposedsuch that prosthetic valve 650 is disposed approximately at the locationof the native aortic valve with proximal end 646 of frame 642 separatingthe valve leaflets of the native aortic valve. Distal end 644 of frame642 extends into lumen 613 of frame 612 of anchor stent 610 and is heldin place by the outward radial force of frame 642 and frictional forcesbetween frame 642 of valve component and frame 612 of anchor stent 610.Further, an inner surface of frame 612 and/or an outer surface of frame642 may include locking features such as barbs, anti-migration tabs orother devices known to the art to interconnect with anchor frame 612.For example, and not by way of limitation, barbs 611 shown in FIG. 14Amay extend from an inner surface of anchor stent 610. Further, proximalarm component 620 provides support for anchor stent 610 within theaortic sinuses, as described in more detail below.

FIGS. 15-23 schematically represent a method of delivering and deployingintegrated valve assembly 600 in accordance with an embodiment hereofFIGS. 15-23 are not drawn to scale.

FIG. 15 shows a distal portion of an exemplary delivery system 700 todeliver and deploy integrated valve prosthesis 600. Delivery system 700may be similar to other delivery devices for delivery and deployment ofvalve prostheses. Accordingly, the proximal portion of delivery system700 is not described herein, but may included features such as handlesand knobs to advance delivery system 700, retract sheath 704, andrelease valve component 640 from hub 705. Delivery system 700 mayinclude, among other features, an inner or guidewire shaft 708 whichincludes a guidewire lumen for receiving a guidewire 702, a distal tip701, an outer sheath 704 defining a capsule 703, and a hub 705. Aproximal end of guidewire 702 may be backloaded into the guidewire lumenof inner shaft 708 through a distal opening tip 701. Delivery system 700may be an over-the-wire type catheter, or a rapid exchange catheter, orother known catheter devices. Outer sheath 704 maintains anchor stent610 and valve component 640 in the radially compressed or deliveryconfiguration during intraluminal delivery through the vasculature, asshown in FIG. 15 . Hub 705 may include grooves or other features to matewith tabs 641 disposed at a distal end of valve component 640. Hub 705and tabs 641 may be features as described, for example and not by way oflimitation, in U.S. Patent Application Publication Nos. 2011/0264203;201/0251675; 2011/0098805; 2010/0049313; and 2009/0287290; and in U.S.Pat. Nos. 8,398,708; 8,052,732; and 6,267,783, each of which isincorporated by reference herein in its entirety. However, deliverysystem 700 may include different features to retain and subsequentlyrelease valve component 640. Further, delivery system 700 mayalternatively include a pusher or stopper as described above withrespect to delivery system 500. Delivery system 700 may also includeother features known to those skilled in the art. Delivery system 700and/or anchor stent 610 may also include, for example, radiopaquemarkers such that the clinician may determine when delivery system 700and/or anchor stent 610 is in the proper location for deployment.

As described previously with respect to FIG. 5 , a guidewire 702 isadvanced distally, i.e., away from the clinician, through the aorta 400into the aortic sinuses 412 in the region of the aortic valve 414.Guidewire 702 may be introduced through an opening or arteriotomythrough the wall of femoral artery in the groin region of the patient bymethods known to those skilled in the art, such as, but not limited to,the Seldinger technique. Guidewire 702 is advanced into the descending(or abdominal) aorta 406, the aortic arch 404, and the ascending aorta402. Although FIGS. 15-23 show a retrograde percutaneous femoralprocedure, it is not meant to limit the method of use and otherprocedural methods may be used. For example, and not by way oflimitation, retrograde percutaneous implantation via subclavian/axillaryroutes, direct apical puncture, and the use of direct aortic access viaeither ministernotomy or right anterior thoracotomy may also be used.

Delivery system 700 is advanced over guidewire 702, as shown in FIG. 16. Once delivery system 700 has been advanced to the desired location,such as when proximal end 616 of anchor stent is generally aligned withthe sinotubular junction 413, outer sheath 704 is retracted proximally,i.e., towards the clinician, as shown in FIG. 17 . As outer sheath 704is retracted, proximal arm component 620 expands radially outward, asshown in FIG. 17 . Delivery system 700 is then advanced distally, i.e.,away from clinician, until proximal arm component 620 bottoms at thenadir of the aortic valve leaflets 117, as shown in FIG. 18 .

Next, anchor stent 610 is deployed in the aorta near the sinotubularjunction 413 by further retracting proximally, i.e., towards theclinician, outer sheath 704 such that tubular frame member 612 expandsfrom the radially compressed configuration to a radially expandedconfiguration engaging an inner wall surface of the ascending aorta, asshown in FIG. 19 .

Although proximal arm component 620 is shown in FIGS. 18-23 as havingarms 622, 624, 626 extending to an area near the base of leaflets 414,those skilled in the art would recognize that arms 622, 624, 626 may beshorter such that they engage the sinuses 412 at a location nearer tosinotubular junction 413 than shown in FIGS. 18-23 .

As can be seen in FIG. 19 , proximal arm component 620 is in theradially expanded configuration such that it flares outwardly from frame612 and engages the aortic sinuses 412, and frame 612 is in the radiallyexpanded configuration such that it engages the inner wall of theascending aorta 402.

Outer sheath 704 is further retracted proximally, i.e., towards theclinician, to deploy tethers 602 and skirt 608 from outer sheath 704, asshown in FIG. 20 . As shown in FIG. 20 , tethers 602 and skirt 608 aredisposed distal of anchor stent 610 and are not constrained by sheath704. Tip 701 may then be retracted to near the distal end of sheath 704,as shown in FIG. 20 .

With outer sheath 704 retracted such that anchor stent 610 is deployedin the aorta 400 and tethers 602 and skirt 608 are released from outersheath 704, delivery system 700 is advanced distally, i.e., away fromthe clinician, through lumen 613 of anchor frame 612, pulling skirt 608and tethers 602 through lumen 613, effectively flipping the direction oftethers 602 and skirt 608. Accordingly, whereas tethers 602 and skirt608 in FIGS. 19-20 extend in a first direction 720 from anchor stent 610towards valve component 640, tethers 602 and skirt 608 in FIGS. 21-23extend in a second direction 722 from anchor stent 610 towards valvecomponent 640. Second direction 722 is generally opposite firstdirection 720. The term “generally opposite” with respect to directionsdescribed herein and terms similar thereto, as used herein, is not sonarrow as to mean 180 degrees difference in direction. Instead, the term“generally opposite” with respect to direction means that a componentincludes a vector component in the first direction, the direction whichis generally opposite includes a vector component in the oppositedirection. Thus, the tethers 602 and skirt 608 in the first direction720 may be within 45 degrees of the first direction 720 and the second,generally opposite direction 722 may be within 135 degrees to 225degrees of the first direction 720. Delivery system 700 is advanceddistally, i.e., away from the clinician, until tethers 602 and skirt 608are taut. Tautness of tethers 602 and skirt 608 correctly positionsvalve component 640 for deployment at desired location, such as near thenative aortic valve leaflets 414 and proximal end 646 of frame 642 beinggenerally aligned with the aortic annulus 415, as shown in FIG. 21

Sheath 704 is then further retracted proximally, i.e., towards theclinician, to deploy frame 642 of valve component 640. Frame 642 expandsradially outward to the radially expanded or deployed configuration, asshown in FIGS. 22-23 . As frame 642 expands, frame 642 separates theleaflets of native valve 414, as shown in FIGS. 22-23 . Proximal end 646of frame 642 engages the inner wall of the annulus 415, with skirt 608disposed between frame 642 and the annulus 415. Dist end 644 of frame642 engages an inner surface of anchor frame 612, as shown in FIGS.22-23 .

With integrated valve prosthesis 600 fully deployed, delivery system 700and guidewire 702 may be retracted proximally, i.e., towards theclinician, and removed in a manner consistent with current proceduresknow to those knowledgeable in the art. Integrated valve prosthesis 600remains in the fully deployed configuration as shown in FIG. 23 . FIGS.16-23 show lateral gaps between the different parts which are disposedadjacent to each other. These gaps are shown for clarity such that thedifferent parts of the integrated valve prosthesis and the heart valvemay be seen. It is understood than many of these parts will abutdirectly against each other due to the radially outward forces of anchorstent 610 and valve frame 642.

Although some examples of advantages have been described above, theseare non-limiting in that other advantages of the integrated valveassembly 300/320/600 would be apparent to those skilled in the art.

It will also be understood that each feature of each embodimentdiscussed herein, and of each reference cited herein, can be used incombination with the features of any other embodiment. All patents andpublications discussed herein are incorporated by reference herein intheir entirety.

While various embodiments according to the present invention have beendescribed above, it should be understood that they have been presentedby way of illustration and example only, and not limitation. It will beapparent to persons skilled in the relevant art that various changes inform and detail can be made therein without departing from the spiritand scope of the invention. Thus, the breadth and scope of the presentinvention should not be limited by any of the above-described exemplaryembodiments, but should be defined only in accordance with the appendedclaims and their equivalents. It will also be understood that eachfeature of each embodiment discussed herein, and of each reference citedherein, can be used in combination with the features of any otherembodiment

1-17. (canceled)
 18. A method of implanting an integrated valve assemblyat a location of a native valve comprising the steps of: advancing theintegrated valve assembly in a radially compressed deliveryconfiguration to the location of the native valve, wherein theintegrated valve assembly comprises an anchor stent, a valve componentincluding a valve frame and a prosthetic valve, and a tether componenthaving a first end coupled to the anchor stent and a second end coupledto the valve component, wherein in the radially compressed deliveryconfiguration the tether component extends in a first direction from theanchor stent to the valve component; deploying the anchor stent from theradially compressed configuration to a radially expanded configurationat a location within an annulus of the native valve; advancing the valvecomponent in the delivery configuration in a second direction oppositethe first direction through at least a portion of the anchor stent suchthat the tether component extends in the second direction from theanchor stent to the valve component; and deploying the valve componentsuch that the valve frame expands from the radially compressed deliveryconfiguration to a radially expanded configuration with a proximalportion of the valve frame engaging an inner surface of the anchorstent.
 19. The method of claim 18, wherein the step of advancing thevalve component in the delivery configuration through at least a portionof the anchor stent comprises advancing the valve component until thetether component becomes taught such that a length of the tether sets alocation for the deployed valve component.
 20. The method of claim 18,wherein the tether component comprises a plurality of tethers.
 21. Themethod of claim 18, wherein the tether component comprises a tubularskirt, the tubular skirt being configured such that the step ofadvancing the valve component disposes the tubular skirt between theanchor stent and the valve frame.
 22. The method of claim 21, whereinthe step of advancing the valve component causes the tubular skirt tofold such that a portion of the skirt extends proximal of the anchorstent and wherein the step of deploying the valve component causes theportion of the tubular skirt extending proximal of the anchor stent toextend radially outward to seal the skirt against tissue of the heart.23-28. (canceled)
 29. A delivery system comprising: an inner shaft; anouter sheath disposed over the inner shaft, the outer sheath beingretractable relative to the inner shaft; and a valve prosthesis assemblydisposed within the outer sheath of the delivery system, the valveprosthesis including an anchor stent and a valve component, the valvecomponent including a valve frame and a prosthetic valve disposed withinand coupled to the valve frame, wherein the anchor stent is disposeddistal of the valve component within the outer sheath.
 30. The deliverysystem of claim 29, further comprising a tether component coupled to adistal end of the anchor stent and a proximal end of the valve frame.31. The delivery system of claim 30, wherein the tether componentcomprises a plurality of tethers.
 32. The delivery system of claim 30,wherein the tether component comprises a skirt.
 33. The delivery systemof claim 30, wherein the tether component comprises a plurality oftethers, further comprising a tubular skirt coupling the tethers to thevalve component.
 34. The delivery system of claim 29, wherein the anchorstent further comprises a proximal arm component, extending from aproximal end of the anchor stent, the proximal arm component configuredto be deployed in the sinuses of the aortic valve.
 35. The deliverysystem of claim 29, further comprising a pusher disposed proximal of thevalve component within the outer sheath.